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Jpn J Pharmacol. 2000 Feb;82(2):130-7.

Antinociception induced by amitriptyline and imipramine is mediated by alpha2A-adrenoceptors.

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  • 1Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.

Abstract

The involvement of alpha2-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using the hot-plate and abdominal constriction tests. The antinociception produced by amitriptyline (15 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.) was prevented by reserpine (2 mg/kg, i.p.) and yohimbine (3-10 mg/kg, i.p.) but not by naloxone (1 mg/kg, i.p.), atropine (5 mg/kg, i.p.), CGP 35348 (100 mg/kg, i.p.) and prazosin (1 mg/kg, i.p.). On the basis of the above data, it can be postulated that amitriptyline and imipramine exerted their antinociceptive effect by activation of alpha2-adrenoceptors. Administration of the alpha2A-adrenoceptor antagonist BRL 44408 (1 mg/kg, i.p.) prevented amitriptyline and imipramine antinociception, whereas the alpha2B/C-adrenoceptor antagonist ARC 239 (10 mg/kg, i.p.) was ineffective. These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of alpha2A-adrenoceptors. Neither tricyclic antidepressants nor the antagonists used impaired mouse performance evaluated by the rota-rod and hole-board tests.

PMID:
10877531
[PubMed - indexed for MEDLINE]
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